Changes in Isoprenaline-Induced Endothelium-Dependent and -Independent Relaxations of Aorta in Long-Term STZ-Diabetic Rats: Reversal Effect of Dietary Vitamin E

Abstract

1. The present study concerns in vitro isoprenaline (ISO)-induced relaxation of aortic rings of long-term streptozotocin (STZ)-diabetic and nondiabetic rats, both with and without dietary vitamin E supplementation. 2. Incubation with propranolol, N G-nitro- L-arginine methyl ester and methylene blue, as well as absence of endothelium, all negatively affect the ISO-induced relaxations. 3. Thiobarbituric acid reactivity levels used as an index of lipid peroxidation are elevated in the aorta by diabetes. Four months of STZ-diabetes results in a significant increase in the ISO-induced relaxations together with endothelial dysfunction in the rat aorta. Diabetes also causes the loss of vascular integrity. 4. Dietary vitamin E supplementation during the last 2 months of diabetes allows normalization of the levels of lipid peroxides. This vitamin also completely reverses the increased sensitivity (pD 2 value) of the aorta to ISO, whereas the maximum ISO-induced relaxations are partially restored after the treatment in diabetic rats. 5. The results suggest that ISO-induced relaxation in the aorta partially depends on the intact endothelium and that the endothelium-dependent relaxant effect of ISO is mediated by endothelium-derived relaxing factor. Results also indicate that abnormal vascular reactivity and structure of the diabetic rat aorta may be related to the increased lipid peroxidation. In conclusion, vitamin E can protect the arterial wall from oxidative stress–induced injury associated with chronic STZ-diabetes and allows normalization of the response to ISO and the structure of the aorta in diabetic rats.